Cancer Immunology, Immunotherapy

, Volume 66, Issue 3, pp 281–298 | Cite as

Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment

  • Dan Ishihara
  • Laurentiu Pop
  • Tsuguhide Takeshima
  • Puneeth Iyengar
  • Raquibul HannanEmail author


Cancer immunotherapy exploits the immune system’s ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT). An increasing number of studies have demonstrated the abscopal effect, an immunologic response occurring in cancer sites distant from irradiated areas. The present work reviews studies on the combination between RT and immunotherapy to induce synergistic and abscopal effects involved in cancer immunomodulation. Further insight into the complex interactions between the immune system and cancer cells in the tumor microenvironment, and their modulation by RT, may reveal the abscopal effect as a clinically relevant and reproducible event leading to improved cancer outcome.


Abscopal effect Tumor immunity Immunotherapy Radiotherapy 



Two dimensional


Three dimensional


Cluster of differentiation


Cytotoxic T lymphocyte


Cytotoxic T-lymphocyte-associated protein 4


Dendritic cell


External beam radiation therapy




Hazard ratio


Intracellular adhesion molecule




Image-guided radiation therapy




Intensity-modulated radiation therapy


Metastatic renal cell carcinoma


Overall survival


Programmed death 1


Programmed death-ligand 1


Prostate-specific antigen


Renal cell carcinoma


Radiation therapy


Stereotactic ablative radiation


Tumor-associated antigen


T cell receptor


Transforming growth factor


Tumor-infiltrating lymphocyte


Regulatory T cell



We thank Dr. Jeffrey Meyer for his contribution to the scientific content of this review and editorial assistance. We thank Dr. Damiana Chiavolini for scientific editing. This review article was not funded.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical statements

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Dan Ishihara
    • 1
  • Laurentiu Pop
    • 2
  • Tsuguhide Takeshima
    • 1
  • Puneeth Iyengar
    • 1
  • Raquibul Hannan
    • 1
    Email author
  1. 1.Department of Radiation OncologyUT Southwestern Medical CenterDallasUSA
  2. 2.Departments of Immunology and MicrobiologyUT Southwestern Medical CenterDallasUSA

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